Olfactory Sensory Neurons Mediate Ultrarapid Antiviral Immune Responses in a TrkA-Dependent Manner

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dc.contributor.authorSepahi, Ali
dc.contributor.authorKraus, Aurora
dc.contributor.authorCasadei, Elisa
dc.contributor.authorJohnston, Christopher A.
dc.contributor.authorGalindo-Villegas, Jorge
dc.contributor.authorKelly, Cecelia
dc.contributor.authorGarcia-Moreno, Diana
dc.contributor.authorMunoz, Pilar
dc.contributor.authorMulero, Victoriano
dc.contributor.authorHuertas, Mar
dc.contributor.authorSalinas, Irene
dc.date.accessioned2020-03-13T14:32:05Z
dc.date.available2020-03-13T14:32:05Z
dc.date.issued2019-06-18
dc.description.abstractThe nervous system regulates host immunity in complex ways. Vertebrate olfactory sensory neurons (OSNs) are located in direct contact with pathogens; however, OSNs' ability to detect danger and initiate immune responses is unclear. We report that nasal delivery of rhabdoviruses induces apoptosis in crypt OSNs via the interaction of the OSN TrkA receptor with the viral glycoprotein in teleost fish. This signal results in electrical activation of neurons and very rapid proinflammatory responses in the olfactory organ (OO), but dampened inflammation in the olfactory bulb (OB). CD8α+ cells infiltrate the OO within minutes of nasal viral delivery, and TrkA blocking, but not caspase-3 blocking, abrogates this response. Infiltrating CD8α+ cells were TCRαβ T cells with a nonconventional phenotype that originated from the microvasculature surrounding the OB and not the periphery. Nasal delivery of viral glycoprotein (G protein) recapitulated the immune responses observed with the whole virus, and antibody blocking of viral G protein abrogated these responses. Ablation of crypt neurons in zebrafish resulted in increased susceptibility to rhabdoviruses. These results indicate a function for OSNs as a first layer of pathogen detection in vertebrates and as orchestrators of nasal-CNS antiviral immune responses.
dc.description.departmentBiology
dc.formatText
dc.format.extent9 pages
dc.format.medium1 file (.pdf)
dc.identifier.citationSepahi, A., Kraus, A., Casadei, E., Johnston, C. A., Galindo-Villegas, J., Kelly, C., García-Moreno, D., Muñoz, P., Mulero, V., Huertas, M., Salinas, I. (2019). Olfactory sensory neurons mediate ultrarapid antiviral immune responses in a TrkA-dependent manner. Proceedings of the National Academy of Sciences of the United States of America, 116(25), pp. 12428–12436.
dc.identifier.doihttps://doi.org/10.1073/pnas.1900083116
dc.identifier.issn1091-6490
dc.identifier.urihttps://hdl.handle.net/10877/9441
dc.language.isoen
dc.publisherNational Academy of Sciences
dc.sourceProceedings of the National Academy of Sciences of the United States of America, 2019, Vol. 116, No. 25, pp. 12428–12436.
dc.subjectneuroimmunology
dc.subjectolfactory sensory neurons
dc.subjectteleost
dc.subjectviral immunity
dc.subjectTrkA
dc.subjectBiology
dc.titleOlfactory Sensory Neurons Mediate Ultrarapid Antiviral Immune Responses in a TrkA-Dependent Manner
dc.typeArticle

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